PMID- 25585624
OWN - NLM
STAT- MEDLINE
DCOM- 20160419
LR  - 20220330
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 240
IP  - 9
DP  - 2015 Sep
TI  - Role of the monocyte chemoattractant protein-1/C-C chemokine receptor 2 signaling 
      pathway in transient receptor potential vanilloid type 1 ablation-induced renal 
      injury in salt-sensitive hypertension.
PG  - 1223-34
LID - 10.1177/1535370214565970 [doi]
AB  - Our recent studies indicate that the transient receptor potential vanilloid type 
      1 (TRPV1) channel may act as a potential regulator of monocyte/macrophage 
      recruitment to reduce renal injury in salt-sensitive hypertension. This study 
      tests the hypothesis that deletion of TRPV1 exaggerates salt-sensitive 
      hypertension-induced renal injury due to enhanced inflammatory responses via 
      monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 
      (CCR2)-dependent pathways. Wild type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice 
      were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt 
      treatment for four weeks with or without the selective CCR2 antagonist, RS504393. 
      DOCA-salt treatment increased systolic blood pressure (SBP) to the same degree in 
      both strains, but increased urinary excretion of albumin and 8-isoprostane and 
      decreased creatinine clearance with greater magnitude in TRPV1(-/-) mice compared 
      to WT mice. DOCA-salt treatment also caused renal glomerulosclerosis, 
      tubulointerstitial injury, collagen deposition, monocyte/macrophage infiltration, 
      proinflammatory cytokine and chemokine production, and NF-kappaB activation in 
      greater degree in TRPV1(-/-) mice compared to WT mice. Blockade of the CCR2 with 
      RS504393 (4 mg/kg/day) had no effect on SBP in DOCA-salt-treated WT or TRPV1(-/-) 
      mice compared to their respective controls. However, treatment with RS504393 
      ameliorated renal dysfunction and morphological damage, and prevented the 
      increase in monocyte/macrophage infiltration, cytokine/chemokine production, and 
      NF-kappaB activity in both DOCA-salt hypertensive strains with a greater effect in 
      DOCA-salt-treated TRPV1(-/-) mice compared to DOCA-salt-treated WT mice. No 
      differences in CCR2 protein expression in kidney were found between 
      DOCA-salt-treated WT and TRPV1(-/-) mice with or without RS504393 treatment. Our 
      studies for the first time indicate that deletion of TRPV1 aggravated renal 
      injury in salt-sensitive hypertension via enhancing MCP-1/CCR2 
      signaling-dependent inflammatory responses.
CI  - (c) 2015 by the Society for Experimental Biology and Medicine.
FAU - Wang, Youping
AU  - Wang Y
AD  - Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan 
      University of Traditional Chinese Medicine, Zhengzhou 450000, China 
      wangyp8@163.com.
FAU - Zhu, Mingjun
AU  - Zhu M
AD  - Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan 
      University of Traditional Chinese Medicine, Zhengzhou 450000, China.
FAU - Xu, Hui
AU  - Xu H
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
FAU - Cui, Lin
AU  - Cui L
AD  - Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan 
      University of Traditional Chinese Medicine, Zhengzhou 450000, China.
FAU - Liu, Weihong
AU  - Liu W
AD  - Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan 
      University of Traditional Chinese Medicine, Zhengzhou 450000, China.
FAU - Wang, Xiaoxiao
AU  - Wang X
AD  - Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan 
      University of Traditional Chinese Medicine, Zhengzhou 450000, China.
FAU - Shen, Si
AU  - Shen S
AD  - Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan 
      University of Traditional Chinese Medicine, Zhengzhou 450000, China.
FAU - Wang, Donna H
AU  - Wang DH
AD  - Department of Medicine, Michigan State University, East Lansing, MI 48824, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150113
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Benzoxazines)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RS 504393)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Sodium Chloride, Dietary)
RN  - 0 (Spiro Compounds)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, mouse)
RN  - 6E0A168OB8 (Desoxycorticosterone Acetate)
SB  - IM
MH  - Animals
MH  - Benzoxazines/pharmacology
MH  - Body Weight/drug effects
MH  - Chemokine CCL2/*metabolism
MH  - Desoxycorticosterone Acetate/administration & dosage
MH  - Hypertension/etiology/*metabolism/pathology
MH  - Kidney/*injuries/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Organ Size/drug effects
MH  - Receptors, CCR2/antagonists & inhibitors/*metabolism
MH  - Signal Transduction
MH  - Sodium Chloride, Dietary/administration & dosage
MH  - Spiro Compounds/pharmacology
MH  - TRPV Cation Channels/*deficiency/genetics
PMC - PMC4935354
OTO - NOTNLM
OT  - Transient receptor potential vanilloid type 1 channel
OT  - chemokine receptor 2
OT  - deoxycorticosterone acetate-salt hypertension
OT  - mice
OT  - renal injury
EDAT- 2015/01/15 06:00
MHDA- 2016/04/20 06:00
PMCR- 2016/03/01
CRDT- 2015/01/15 06:00
PHST- 2014/08/15 00:00 [received]
PHST- 2014/11/12 00:00 [accepted]
PHST- 2015/01/15 06:00 [entrez]
PHST- 2015/01/15 06:00 [pubmed]
PHST- 2016/04/20 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - 1535370214565970 [pii]
AID - 10.1177_1535370214565970 [pii]
AID - 10.1177/1535370214565970 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2015 Sep;240(9):1223-34. doi: 10.1177/1535370214565970. 
      Epub 2015 Jan 13.